Early-onset Temporal Lobe Epilepsy Research Articles

Infantile status epilepticus disrupts myelin development

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.

Psychoses of epilepsy – “Acute attacks of insanity”. What literature says and how we act

IntroductionPatients with epilepsy seem particularly liable to certain major psychiatric disorders. Prevalence of schizophrenia within an epileptic population varies between 3% and 7% (1% in general population). The aetiology is possibly multifactorial (drugs and neurosurgery).ObjectivesTo study comorbidity between psychoses and epilepsy and management in the literature and in our patients.AimsTo analyze factors that might influence the onset of psychoses within an epileptic population and how this potential association could influence our practice.MethodsPubMed search was conducted with interest in psychoses of epilepsy, pharmacology, and comorbidity. Up to 10 variables related with factors influencing psychotic episodes that required hospital admission in three patients with epilepsy were studied.ResultsUnlike published data, our patients did not have postictal psychoses. All cases had early onset temporal lobe epilepsy with no seizure activity since diagnosis (more than 20 years). No family history of either epilepsy or psychoses. Management included lamotrigine, oxcarbazepine, carbamazepine, zonisamide, and levetiracetam in conventional doses. The psychosis, which comprised affective, schizophrenic, and confusional elements, lasted longer and was more troublesome than psychosis in non-epileptic patients. Response to neuroleptics was poorer than in non-epileptic patients with psychoses. Consultation with Neurology Unit resulted in end of treatment with zonisamide and levetiracetam.ConclusionsLess than perfect evidence suggests the association between psychosis and epilepsy. In our patients, no postictal cases were recorded. Management showed poorer effect of neuroleptics when compared with non-epileptics, and zonisamide and levetiracetam were changed for other drugs with presumably lower association with psychoses.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups

In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20years in three major German epilepsy centers was reviewed. Age at surgery and duration of epilepsy, which was differentiated according to histopathology (AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately. Of all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7years and the duration of epilepsy until surgery increased by 5years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery. During the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS (mTLE+AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease-modifying factors which have changed the incidence of classical mTLE+AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery.

Language reorganization in early onset temporal lobe epilepsy

Behavioral and functional magnetic resonance imaging (fMRI) studies have consistently shown abnormalities of language function or cortical organization in patients with well-established temporal lobe epilepsy (TLE). However, whether these changes are present in new-onset TLE has not been studied to date. Studying such changes in new-onset TLE would provide valuable insight into the timing and factors that affect language deficits in TLE and may unmask fundamental differences in brain organization in persons who have TLE and those who do not.

Neurodevelopmental disruption in early-onset temporal lobe epilepsy: Evidence from a voxel-based morphometry study

Childhood onset of epilepsy has long been associated with an adverse impact on brain development and cognition. In this study it is proposed that earlier (vs later) onset of temporal lobe epilepsy (TLE) has a negative developmental impact on distant brain structures. One hundred ten patients with TLE were assigned to early (≤ 14 years, N = 58) and late (> 15 years, N = 52) age at onset of epilepsy groups. Voxel-based morphometry revealed onset-dependent abnormalities (in terms of a gray matter excess in the early-onset group), which were found mainly in frontal regions. An excess of gray matter is not a usual finding in TLE. However, within a neurodevelopmental framework, retained gray matter is discussed as reflecting neurodevelopmental disruption. The findings indicate the importance of quantitative MRI for the detection of subtle secondary abnormalities in focal TLE and once more underline the importance of early seizure management in children with intractable TLE.

The nature and extent of cerebellar atrophy in chronic temporal lobe epilepsy

Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p's > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

Ictal vocalizations occur more often in temporal lobe epilepsy with dominant (left‐sided) epileptogenic zone

To investigate the lateralization value of ictal vocalizations in temporal lobe epilepsy (TLE). We reviewed video-recordings of 97 patients who had undergone presurgical evaluation programs with video-EEG (electroencephalography)-recorded complex partial seizures (CPS) and high-resolution magnetic resonance imaging (MRI). All patients had surgery due to TLE and became seizure-free. In 57 patients, determination of speech dominance was necessary by using Wada tests or functional MRI (fMRI). To reevaluate the archived seizures, we reviewed one to three consecutively recorded CPS of each patient. Altogether 223 archived seizures were analyzed. Ictal vocalization was considered to be present in a particular patient if it occurred in at least one of the recorded seizures. Ictal vocalizations occurred in 22 patients. They occurred in 37% of left-sided and in 11% of right-sided patients with TLE (p = 0.003). In patients with determined speech lateralization, ictal vocalizations occurred in 37% of the dominant and in 14% in patients with nondominant epileptogenic zone (p = 0.04). In patients with ictal vocalizations, epilepsy began at age 8.7 +/- 6, whereas in the remaining patients, epilepsy started at age 14.0 +/- 9 (p = 0.017). Logistic regression showed that both hemispheric dominance and age at onset were independently associated with pure ictal vocalization (PIV). Ictal vocalization is a frequent phenomenon, occurring in 23% of patients with TLE. It is more often associated with left-sided and early onset TLE. Our results may improve the lateralization of the epileptogenic zone and suggest that nonspeech vocalizations in humans are related to the dominant (left-sided) hemisphere. Our study is a further argument that there are different subtypes of TLE depending on the age at onset.

Age at onset of epilepsy as a determinant of intellectual impairment in temporal lobe epilepsy

Intellectual impairment in addition to memory problems in temporal lobe epilepsy (TLE) has been postulated to be a result of a mental decline caused by chronic epilepsy. Longer duration, however, is often confounded with earlier age at onset of epilepsy (AOE). IQ and memory were evaluated in 188 patients (age > 16) with TLE with an AOE before age 14 ( N = 91) or after age 15 ( N = 97). Earlier AOE did not differentially affect memory aspects more associated with temporomesial structures, but it negatively affected IQ and aspects of memory that are more related to temporolateral and extratemporal lobe structures. As earlier AOE was also associated with lower educational levels and because one may not assume that these are lost with chronicity of epilepsy, the results can be interpreted as reflecting developmental hindrance of extratemporal lobe functions in early-onset TLE rather than cognitive decline due to a longer duration of epilepsy.

Impaired facial expression recognition in children with temporal lobe epilepsy: Impact of early seizure onset on fear recognition

The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8–16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and eight had fronto-central epilepsy (FCE). Each was matched on age and gender with a control subject. Subjects were asked to label the emotions expressed in pictures of children's faces miming five basic emotions (happiness, sadness, fear, disgust and anger) or neutrality (no emotion). All groups of children with epilepsy performed less well than controls. Patterns of impairment differed according to the topography of the epilepsy: the left-TLE (LTLE) group was impaired in recognizing fear and neutrality, the right-TLE (RTLE) group was impaired in recognizing disgust and, the FCE group was impaired in recognizing happiness. We clearly demonstrated that early seizure onset is associated with poor recognition of facial expression of emotion in TLE group, particularly for fear. Although right-TLE and left-TLE subjects were both impaired in the recognition of facial emotion, their psychosocial adjustment, as measured by the CBCL questionnaire [Achenbach, T. M. (1991). Manual for the Child Behavior Checklist and Youth Self-report. Burlington, VT: University of Vermont Department of Psychiatry], showed that poor recognition of fearful expressions was related to behavioral disorders only in children with right-TLE. Our study demonstrates for the first time that early-onset TLE can compromise the development of recognizing facial expressions of emotion in children and adolescents and suggests a link between impaired fear recognition and behavioral disorders.

Neuropsychology and temporal lobe epilepsy.

The purpose of this article is to review aspects of the neuropsychology of temporal lobe epilepsy. Evidence will be presented to demonstrate that the cognitive consequences of this focal seizure disorder can be more generalized in nature than expected. Consistent with the extratemporal neurocognitive findings, careful quantitative magnetic resonance imaging volumetrics have shown that structural brain changes may be detected outside the temporal lobes. Many factors can potentially affect cognition and brain structure. We focus on the potential neurodevelopmental impact of early-onset temporal lobe epilepsy on brain structure and cognition positing that this disorder can have both immediate and lifespan implications for cognition and psychosocial status.

Object naming and semantic knowledge in temporal lobe epilepsy.

Object-naming impairment is common among temporal lobe epilepsy (TLE) patients, but other aspects of semantic memory have received limited attention in this population. This study examined object-naming ability and depth of semantic knowledge in healthy controls (n = 29) and patients with early onset TLE (n = 21). After administration of the Boston Naming Test (BNT), the authors asked participants to provide detailed definitions of 6 BNT objects. The TLE group demonstrated a significant deficit relative to controls in both object-naming ability and semantic knowledge for the target objects, even after controlling for IQ. In a multiple regression analysis that included other neuropsychological test scores as independent variables, the semantic knowledge score was the only significant predictor of patients' object-naming performance. Thus, at the group level, early onset TLE patients have a semantic knowledge deficit that contributes to dysnomia.

Neuronal activity and the establishment of normal and epileptic circuits during brain development

The question we attempted to address in this chapter is: Do brief but recurrent seizures in early life alter the ontogeny of hippocampal networks in ways that produce epileptic circuits? Results from the tetanus toxin model suggest that this is likely the case. Following seizures in Postnatal Weeks 2 and 3, most adult rats have a focal epilepsy that arises from hippocampus. Recordings from hippocampal slices support this conclusion since they demonstrated the occurrence of spontaneous network discharges in normal artificial cerebrospinal fluid. Moreover, when GABA-A receptor-mediated synaptic transmission was suppressed, slices from adult epileptic rats produced prolonged electrographic seizures which are never observed in control rats. This suggests that hyperexcitable recurrent excitatory networks contribute to hippocampal seizures in this model. In light of this, anatomical results from biocytin-filled neurons were surprising. Results suggest that recurrent axon arbors neither sprout additional branches as a result of seizure activity nor maintain their exuberant branching patterns of early life. Thus, excessive connectivity cannot explain seizure generation. Axon arbors either remodel in normal ways or prune additional collaterals as a result of ongoing epileptiform discharging. At the same time that axon arbors remodel, the dendrites of these cells have decreased dendritic spine density, suggesting a partial deafferentation. While a complete understanding of the origins of spine loss requires further investigation, we hypothesize that this loss is a product of a partial deafferentation that occurs due to excessive and abnormal selection of synaptic connections. Network-induced heterosynaptic LTD of noncoincidentally active afferants may be one mechanism that leads to a loss of synapses. Moreover, competition among and selection between individual recurrent excitatory synapses may contribute to spine loss as well. The "winners" of this competition, the most potent and effective early-formed recurrent excitatory synapses, are likely key contributors to seizure generation in this model and possibly in humans with early-onset temporal lobe epilepsy.

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

The apolipoprotein E epsilon 4 allele is not associated with early onset temporal lobe epilepsy.

A polymorphism of the apolipoprotein E gene, in particular the epsilon 4 allele (ApoE4), has been associated with impaired neuronal phospholipid metabolism and synapse reorganization and has been implicated in several neurodegenerative disorders. Since selective neuronal cell lose and aberrant axonal reorganization represent hall-marks of Ammon's horn sclerosis (AHS) in patients with chronic temporal lobe epilepsy (TLE), the ApoE polymorphism was studied in 125 patients with TLE. The genotype analysis revealed a frequency of 15.5% for epsilon 4, and 74.8% and 9.8% for epsilon 3 and epsilon 2, respectively. These figures were not significantly different from those reported in the normal European population. In addition, no correlation was found between the ApoE4 allelotype and the age of epilepsy onset, seizure type, febrile seizures, family history of epilepsy, surgical outcome and neuropathological findings in patients with TLE. These data virtually exclude ApoE as a susceptibility gene involved in the pathogenesis of early onset TLE or AHS.

Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep epilepsy in amygdala-kindled kittens.

We previously described a model of spontaneous "sleep epilepsy" in kindled kittens with temporal lobe epilepsy (TLE). We now describe the postkindling course of this model from preadolescence to maturity and suggest pathophysiologic mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic convulsions (GTCs), developed 1h to 4 months after amygdala kindling and persisted to adulthood. At first, GTCs were detected only in sleep; later, convulsions also occurred during wakefulness. Two factors were consistently associated with the sequential onset of sleep and waking GTCs: seizure clusters and anatomic seizure localization. (1) Seizure clusters. Cats with infrequent or unclustered GTCs continued to exhibit "sleep epilepsy," defined by convulsions occurring exclusively during sleep. In contrast, cats with frequent seizure clusters developed recurrent or terminal convulsive status in conjunction with GTCs during waking and sleep. Severe seizure manifestations therefore appeared to contribute to the dissociation of convulsions from the sleep-wake cycle. (2) Anatomical seizure localization. Focal seizure origin appeared to differentiate sleep from waking GTCs. Onset during sleep was first recorded in the kindled amygdala, whereas onset during waking was initially detected outside the temporal lobe. Findings thus suggest secondary "kindling" of multifocal epilepsy. Secondary epileptogenesis is consistent with "transsynaptic" kindling effects. This phenomenon is defined in mature animals by rapid secondary site kindling (transfer) and subtle morphologic changes distal to the stimulating electrode. Transfer may be accentuated by youth, because kittens developed spontaneous seizure foci in previously unstimulated tissue. Moreover, multifocal interactions and diffuse cell loss were implicated as possible mechanisms. Collectively, the findings indicate complications with early onset TLE in kindled cats. Onset during youth can have an unfavorable prognosis, reflected by recurrent status epilepticus and multifocal epilepsy with convulsions distributed throughout the sleep-wake cycle.